3 years ago

Hsp70-associated chaperones have a critical role in buffering protein production costs

Károly Kovács, Tamás Balassa, Dorottya Kalapis, Aladár Pettkó-Szandtner, Edit Rutkai, Zoltán Farkas, Gábor Boross, Éva Klement, Csaba Molnár, Andreea Daraba, Péter Horváth, Ferenc Pál, Béla Szamecz, Balázs Papp, Attila Szvetnik, Karola Almási, Zoltán Bódi, Csaba Pál
Proteins are necessary for cellular growth. Concurrently, however, protein production has high energetic demands associated with transcription and translation. Here, we propose that activity of molecular chaperones shape protein burden, that is the fitness costs associated with expression of unneeded proteins. To test this hypothesis, we performed a genome-wide genetic interaction screen in baker's yeast. Impairment of transcription, translation, and protein folding rendered cells hypersensitive to protein burden. Specifically, deletion of specific regulators of the Hsp70-associated chaperone network increased protein burden. In agreement with expectation, temperature stress, increased mistranslation and a chemical misfolding agent all substantially enhanced protein burden. Finally, unneeded protein perturbed interactions between key components of the Hsp70-Hsp90 network involved in folding of native proteins. We conclude that specific chaperones contribute to protein burden. Our work indicates that by minimizing the damaging impact of gratuitous protein overproduction, chaperones enable tolerance to massive changes in genomic expression.

Publisher URL: https://elifesciences.org/articles/29845

DOI: 10.7554/eLife.29845

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